Pattern Formation and Neuronal Cell Recognition 
in the Drosophila Visual System 
Hermann Steller, Ph.D. — Assistant Investigator 
Dr. Steller is also Associate Professor of Neurobiology at the Massachusetts Institute of Technology and 
Adjunct Assistant Neurobiologist at Massachusetts General Hospital, Boston. He was born in the Federal 
Republic of Germany and received a Diplom in biology from the Johann- Wolf gang- Goethe University, 
Frankfurt. His graduate studies were done with Vincenzo Pirrotta at the European Molecular Biology 
Laboratory and with Ekkehard Bautz at Heidelberg University. His postdoctoral work was done with 
Gerald Rubin in the Department of Biochemistry at the University of California, Berkeley. Dr. Steller is 
currently also a Searle Scholar and a Pew Fellow in the Biomedical Sciences. 
THE overall objective of our research is to un- 
derstand how functional neuronal circuits 
are established and maintained during develop- 
ment. Our current work is focused on three major 
areas. 
Axon Guidance and Neuronal 
Cell Recognition 
We are studying two different stages of visual 
system development to investigate the cellular 
and molecular mechanisms by which axons find 
and recognize their proper synaptic partners. The 
optic nerve of the Drosophila larva is a simple, 
well-described model system. Connectivity de- 
fects of the larval optic nerve can be rapidly and 
reliably detected in mutant embryos by staining 
with neuron-specific antibodies. In addition, a 
simple behavioral test, larval phototaxis, pro- 
vides an assay for functional connections of the 
larval optic nerve. This permits systematic 
screening for mutants with abnormal axonal pro- 
jections, which can be subsequently analyzed in 
detail with respect to defects in axonal guidance, 
target recognition, and synapse formation. 
We have previously identified a gene, discon- 
nected {disco), which is required for establish- 
ing stable connections between the larval optic 
nerve and its target cells in the developing brain. 
We have cloned the disco gene and determined 
its structure, nucleotide sequence, and pattern of 
expression. These studies suggest that disco en- 
codes a transcription factor with autoregulatory 
properties. Consistent with such a function we 
have recently found that disco protein has se- 
quence-specific DNA-binding activity in vitro 
and that two high-affinity binding sites are lo- 
cated very close to the disco transcription unit. 
Ectopic expression of disco protein under an in- 
ducible promoter in transgenic flies results in se- 
vere developmental defects and embryonic lethal- 
ity. These defects include a drastic reduction of 
the axon scaffold and connectivity defects in both 
the peripheral and central nervous systems. We 
are now testing the idea that disco regulates the 
expression of cell adhesion and/or cell recogni- 
tion molecules that are required for the establish- 
ment of stable connections between the larval 
optic nerve and its target cells in the brain. 
More recently we have begun to study axon 
guidance and neuronal cell recognition in the 
adult visual system. The compound eye of Dro- 
sophila consists of approximately 800 repeating 
units called ommatidia. Each ommatidium con- 
tains eight photoreceptor neurons, which repre- 
sent three major cell types that project to differ- 
ent target cells in the optic ganglia. The major 
class of photoreceptors, Rl-6, establishes synap- 
tic connections with neurons in the first optic 
ganglion, the lamina. Photoreceptor axons from 
R7 and R8 project deeper into the brain to differ- 
ent regions of the second ganglion, the medulla. 
Early during visual system development, all eight 
photoreceptor axons from each ommatidium 
grow as a bundle to specific retinotopic positions 
in the developing brain. The growth cones of 
these axons have to navigate over a long distance 
and make a number of highly specific choices. 
We would like to understand what signals 
guide axons to their proper destinations and how 
these signals are generated, received, and inter- 
preted. To address these questions, we have 
screened for mutations that perturb the projec- 
tion pattern of photoreceptor cells at very early 
developmental stages, when axons enter the 
brain. We have found a number of mutants with 
severely abnormal patterns of axon ingrowth. The 
developmental and genetic characterization of 
this material is in progress. 
Role of Innervation for Neurogenesis 
and Survival of Target Cells 
It has been noticed for many years that synaptic 
input can have a profound influence on the fate 
and differentiation of target cells. Cell death in 
the absence of incoming projections is a dramatic 
example of how innervation can affect develop- 
mental decisions, and many neurological dis- 
orders are thought to arise from defective interac- 
tions between neurons and their targets. In 
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